Scientists
are racing towards a future vision in which humans can regrow
failing organs and essentially obtain
immortality. Along the way, they're shooting for the more
obtainable aim of curing a number of diseases (cancer, Alzheimer's,
Parkinson's, and paralysis, to list but a few) using stem cells.

A
critical problem though is how to direct
stem cells to become the proper tissue type. Within
the human body, there are a rich variety of cells -- endothelial
cells, muscle cells, blood cells, osteoblasts (bone), and nerve cells
to name but a few. At some point in the development of the
human body, these cell lines were created by a biochemical signal
which instructing stem cells to become the particular cell
type.

Experimentalists at Cambridge University and Rice
bioengineers Oleg Igoshin and Jatin Narula have examined one of these
critical biochemical signals. Based on a computer model
developed at Rice and experiments at Cambridge, they believe that a
trio of regulatory proteins known as the "Scl-Gata2-Fli1 triad"
controls the differentiation of hematopoietic stem cells (HSCs), the
self-renewing cells the body uses to make new blood cells.

In
healthy adult humans, each day HSCs are responsible for the creation
of 100 billion new white and red blood cells. HSCs are also
capable of "self-renewing" if the bone marrow is
damaged.

The research at Rice delved into looking at the three
regulatory proteins and developing an mathematical model for how they
interacted with HSCs. In their model, the proteins act as a
bistable switch, with two states -- "replenish HSC" and
"differentiate". The system ignores extraneous
signals and throws the switch only when a signal persisted.

Igoshin,
an assistant professor in bioengineering at Rice, comments,
"We don't yet have the experimental verification that this is
the master-level regulator for HSCs, but based on our model, we can
say that it has all the properties that we would expect to find in a
master-level regulator."

Jatin Narula, a Rice graduate
student, adds, "In examining the results from the model, we
found the triad did have the characteristics of a master regulator.
The first time it's switched on, all the cells stay on. It also
handles deactivation in a controlled manner, so that some cells
differentiate and get deactivated and others don't. Finally, it has
the ability to discern whether or not the level of signal is present
only for a short burst or for a significantly long time."

Rice
researchers hope that the regulatory triad motif reappears in other
types of stem cells, possibly leading to more breakthroughs.

The
results of the study are published in
the journal PLoS
Computational Biology.

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